We are using quantitative immunochemical methods to locate the antigenic determinants on hemoglobins A and S. We have changed the metal in the porphyrin of the heme group in both hemoglobins and are studying these reconstituted hemoglobins by quantitative precipitin and radioimmunoassay to see if any significant conformational changes have been induced. These studies will allow us to detect subtle changes in the conformation of hemoglobins with zinc, copper, cobalt, manganese and nickel metalloporphyrins. Further, the metalloporphyrin and the chemical modification studies should allow us to locate antigenic determinants on the hemoglobin molecule. In addition we are studying the effects on the gelation of sickle hemoglobin of the metalloporphyrin substitutes. A solubility assay in buffers of high phosphate concentration is being used for this purpose.